Roywashington3193

The reliability of several density functional theory (DFT) functionals and of the Möller-Plesset second-order perturbation theory calculations with modified basis sets (mp2mod) approach in describing cation-π interactions is systematically investigated by benchmarking their performances with respect to high quality reference CCSD(T) calculations of the binding energies between alkaline cations of varying radius (Na+, K+, Rb+, and Cs+) and three aromatic species (benzene, phenol, and catechol). For this class of noncovalent interaction, mp2mod delivers, on average, results in very good agreement with the reference CCSD(T) data, yet at a very small computational cost, exploiting the reduced dimensions of the modified basis set. Conversely, the tested DFT functionals show a more erratic behavior, with different performances depending on both the investigated system and the combination of the employed functional and basis set. The mp2mod computational convenience is further exploited to extensively sample two-dimensional interaction energy surfaces of all investigated cation-π systems, which allow for a deeper insight on the effect of the increasing number of hydroxyl substituents, revealing the insurgence, upon substitution, of alternative minima, evident in particular for the smaller cations. The present results strongly support for further applications of the mp2mod method to study a larger variety of aromatic/metal cation species, relevant both in biological processes and in technological applications.Intermediate states in protein folding are associated with formation of amyloid fibrils, which are responsible for a number of neurodegenerative diseases. Therefore, prevention of the aggregation of folding intermediates is one of the most important problems to overcome. Recently, we studied the origins and prevention of formation of intermediate states with the example of the Formin binding protein 28 (FBP28) WW domain. We demonstrated that the replacement of Leu26 by Asp26 or Trp26 (in ~15% of the folding trajectories) can alter the folding scenario from three-state folding, a major folding scenario for the FBP28 WW domain (WT) and its mutants, toward two-state or downhill folding at temperatures below the melting point. Here, for a better understanding of the physics of the formation/elimination of intermediates, (i) the dynamics and energetics of formation of β-strands in folding, misfolding and nonfolding trajectories of these mutants (L26D and L26W) is investigated; (ii) the experimental structures of WT, L26D and L26W are analyzed in terms of a kink (heteroclinic standing wave solution) of a generalized discrete nonlinear Schrödinger equation. We show that the formation of each β-strand in folding trajectories is accompanied by the emergence of kinks in internal coordinate space as well as a decrease in local free energy. In particular, the decrease in downhill folding trajectory is ~7 kcal/mol, while it varies between 31-48 kcal/mol for the three-state folding trajectory. The kink analyses of the experimental structures give new insights into formation of intermediates, which may become a useful tool for preventing aggregation.Dopamine-derived N6-substituents, compared to N6-(2-phenylethyl), in truncated (N)-methanocarba (bicyclo[3.1.0]hexyl) adenosines favored high A3 adenosine receptor (AR) affinity/selectivity, e.g., C2-phenylethynyl analogue 15 (MRS7591, Ki = 10.9/17.8 nM, at human/mouse A3AR). HOpic chemical structure 15 was a partial agonist in vitro (hA3AR, cAMP inhibition, 31% Emax; mA3AR, [35S]GTP-γ-S binding, 16% Emax) and in vivo and also antagonized hA3AR in vitro. Distal H-bonding substitutions of the N6-(2-phenylethyl) moiety particularly enhanced mA3AR affinity by polar interactions with the extracellular loops, predicted using docking and molecular dynamics simulation with newly constructed mA3AR and hA3AR homology models. These hybrid models were based on an inactive antagonist-bound hA1AR structure for the upper part of TM2 and an agonist-bound hA2AAR structure for the remaining TM portions. These species-independent A3AR-selective nucleosides are low efficacy partial agonists and novel, nuanced modulators of the A3AR, a drug target of growing interest.The chiral-induced spin selectivity (CISS) effect, which describes the spin-filtering ability of diamagnetic structures like DNA or peptides having chiral symmetry, has emerged in the past years as the central mechanism behind a number of important phenomena, like long-range biological electron transfer, enantiospecific electrocatalysis, and molecular recognition. Also, CISS-induced spin polarization has a considerable promise for new spintronic devices and the design of quantum materials. The CISS effect is attributed to spin-orbit coupling, but a sound theoretical understanding of the surprising magnitude of this effect in molecules without heavy atoms is currently lacking. We are taking an essential step into this direction by analyzing the importance of imaginary terms in the Hamiltonian as a necessary condition for nonvanishing spin polarization in helical structures. On the basis of first-principles calculations and analytical considerations, we perform a symmetry analysis of the key quantities determining transport probabilities of electrons of different spin orientations. These imaginary terms originate from the spin-orbit coupling, and they preserve the Hermitian nature of the Hamiltonian. Hence, they are not related to the breaking of time-reversal symmetry resulting from the fact that molecules are open systems in a junction. Our symmetry analysis helps to identify essential constraints in the theoretical description of the CISS effect. We further draw an analogy with the appearance of imaginary terms in simple models of barrier scattering, which may help understanding the unusually effective long-range electron transfer in biological systems.This study investigated the changes in enzyme activity and gene expression in reactive oxygen species (ROS) and fatty acid metabolism in Docteur Jules Guyot pears after acibenzolar-S-methyl (ASM) treatment to elucidate the role of ROS and fatty acid metabolism in senescence. The results demonstrated that applying ASM postharvest significantly suppressed H2O2 content and enhanced catalase and superoxide dismutase activities in pears. Ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase, and monodehydroascorbate reductase activities and the reduced glutathione content in pears were also induced by ASM. Postharvest ASM dipping remarkably enhanced PcSOD, PcCAT, PcAPX, and PcDHAR expressions and fatty acid synthetase activity in pears. Postharvest applying ASM significantly decreased malondialdehyde content and lipoxygenase, hydroperoxidelyase, alcohol dehydrogenase, and alcohol acyltransferase activities in pears. ASM distinctly inhibited PcPLD, PcLOX, PcHPL, PcADH, and PcAAT expressions in pears.